Protocol for the Examination of Specimens From Patients With

Malignant Pleural Mesothelioma

Version: 4.1.0.0
Protocol Posting Date: June 2021
CAP Laboratory Accreditation Program Protocol Required Use Date: March 2022
The changes included in this current protocol version affect accreditation requirements. The new deadline
for implementing this protocol version is reflected in the above accreditation date.

For accreditation purposes, this protocol should be used for the following procedures AND tumor
types:
Procedure Description
Resection Includes extrapleural pneumonectomy, pleurectomy, and decortication
procedures
Tumor Type Description
Mesothelioma

This protocol is NOT required for accreditation purposes for the following:
Procedure
Biopsy
Primary resection specimen with no residual cancer (eg, following neoadjuvant therapy)
Cytologic specimens

The following tumor types should NOT be reported using this protocol:
Tumor Type
Solitary fibrous tumor
Peritoneal mesothelioma
Lymphoma (consider the Hodgkin or non-Hodgkin Lymphoma protocols)
Sarcoma (consider the Soft Tissue protocol)

Authors
Frank Schneider, MD*; Anja Roden, MD; Sanja Dacic, MD, PhD; Thomas P. Baker, MD, FCAP.

With guidance from the CAP Cancer and CAP Pathology Electronic Reporting Committees.
* Denotes primary author.

© 2021 College of American Pathologists (CAP). All rights reserved. For Terms of Use please visit www.cap.org/cancerprotocols . 1
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Accreditation Requirements
This protocol can be utilized for a variety of procedures and tumor types for clinical care purposes. For
accreditation purposes, only the definitive primary cancer resection specimen is required to have the core
and conditional data elements reported in a synoptic format.
 Core data elements are required in reports to adequately describe appropriate malignancies. For
accreditation purposes, essential data elements must be reported in all instances, even if the
response is “not applicable” or “cannot be determined.”
 Conditional data elements are only required to be reported if applicable as delineated in the
protocol. For instance, the total number of lymph nodes examined must be reported, but only if
nodes are present in the specimen.
 Optional data elements are identified with “+” and although not required for CAP accreditation
purposes, may be considered for reporting as determined by local practice standards.
The use of this protocol is not required for recurrent tumors or for metastatic tumors that are resected at a
different time than the primary tumor. Use of this protocol is also not required for pathology reviews
performed at a second institution (ie, secondary consultation, second opinion, or review of outside case at
second institution).

Synoptic Reporting
All core and conditionally required data elements outlined on the surgical case summary from this cancer
protocol must be displayed in synoptic report format. Synoptic format is defined as:
 Data element: followed by its answer (response), outline format without the paired Data element:
Response format is NOT considered synoptic.
 The data element should be represented in the report as it is listed in the case summary. The
response for any data element may be modified from those listed in the case summary, including
“Cannot be determined” if appropriate.
 Each diagnostic parameter pair (Data element: Response) is listed on a separate line or in a
tabular format to achieve visual separation. The following exceptions are allowed to be listed on
one line:
o Anatomic site or specimen, laterality, and procedure
o Pathologic Stage Classification (pTNM) elements
o Negative margins, as long as all negative margins are specifically enumerated where
applicable
 The synoptic portion of the report can appear in the diagnosis section of the pathology report, at
the end of the report or in a separate section, but all Data element: Responses must be listed
together in one location
Organizations and pathologists may choose to list the required elements in any order, use additional
methods in order to enhance or achieve visual separation, or add optional items within the synoptic
report. The report may have required elements in a summary format elsewhere in the report IN
ADDITION TO but not as replacement for the synoptic report ie, all required elements must be in the
synoptic portion of the report in the format defined above.

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Summary of Changes

v 4.1.0.0
 General Reformatting
 New WHO 5th Edition Histological Updates
 Added Nuclear Atypia Score
 Added Mitotic Count Score
 Added Nuclear Grade
 Added Necrosis
 Added Histologic Grade
 Revised Treatment Effect
 Revised Margins Section
 Revised Lymph Node Section
 Removed pNX Staging Classification

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Reporting Template

Protocol Posting Date: June 2021

Select a single response unless otherwise indicated.

CASE SUMMARY: (MALIGNANT PLEURAL MESOTHELIOMA)

Standard(s): AJCC-UICC 8

CLINICAL

+Clinical History (select all that apply)

___ Neoadjuvant therapy performed (specify type, if known): _________________
___ Other (specify): _________________

SPECIMEN (Note A)

Procedure (select all that apply)

___ Extrapleural pneumonectomy
___ Extended pleurectomy / decortication
___ Pleurectomy / decortication
___ Partial pleurectomy
___ Other (specify): _________________
___ Not specified

Specimen Laterality
___ Right
___ Left
___ Not specified

TUMOR

Tumor Focality (Note D)

___ Localized
___ Diffuse
___ Cannot be determined: _________________

Tumor Site (select all that apply)

___ Parietal pleura: _________________
___ Visceral pleura: _________________
___ Diaphragm: _________________
___ Other (specify): _________________
___ Not specified

+Tumor Size (for localized tumors only)

___ Greatest dimension in Centimeters (cm): _________________ cm
+Additional Dimension in Centimeters (cm): ____ x ____ cm
___ Cannot be determined (explain): _________________

Histologic Type (Note B)

___ Epithelioid mesothelioma

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+Architectural Pattern (may include percentages totaling 100%) (select all that apply)
___ Tubulopapillary: _________________ %
___ Trabecular: _________________ %
___ Adenomatoid: _________________ %
___ Solid: _________________ %
___ Micropapillary: _________________ %
___ Other (specify): _________________
+Cytological Features (select all that apply)
___ Rhabdoid
___ Deciduoid
___ Small cell
___ Clear cell
___ Signet ring
___ Lymphohistiocytoid
___ Pleomorphic
___ Other (specify): _________________
+Stromal Features (select all that apply)
___ Myxoid predominant
___ Other (specify): _________________
___ Sarcomatoid mesothelioma
+Cytological Features (select all that apply)
___ Lymphohistiocytoid
___ Transitional
___ Pleomorphic
___ Other (specify): _________________
+Stromal Features (select all that apply)
___ Desmoplastic
___ With heterologous differentiation
___ Other (specify): _________________
___ Biphasic mesothelioma
Percentage of Sarcomatoid Pattern
___ Specify percentage: _________________ %
___ Other (specify): _________________
___ Cannot be determined
___ Other histologic type not listed (specify): _________________
___ Cannot be determined (explain): _________________
+Histologic Type Comment: _________________

+Nuclear Atypia Score

___ 1 (mild)
___ 2 (moderate)
___ 3 (severe)
___ Cannot be determined: _________________

+Mitotic Count Score

___ 1 (low, up to 1 mitosis per 2 mm2)
___ 2 (intermediate, 2 to 4 mitoses per 2 mm2)
___ 3 (high, 5 or more mitoses per 2 mm2)
___ Cannot be determined: _________________

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+Nuclear Grade (sum of nuclear atypia and mitotic count scores)

___ 1 (sum score of 2 or 3)
___ 2 (sum score of 4 or 5)
___ 3 (sum score of 6)
___ Cannot be determined: _________________

+Necrosis
___ Not identified
___ Present
___ Cannot be determined: _________________

Histologic Grade
___ Low grade (nuclear grades 1 and 2 without necrosis)
___ High grade (nuclear grade 2 with necrosis, or nuclear grade 3 with or without necrosis)
___ Cannot be determined: _________________

Tumor Extent (Note E) (select all that apply)

___ Limited to parietal pleura without involvement of ipsilateral visceral, mediastinal, or diaphragmatic
pleura
___ Limited to parietal pleura with focal involvement of ipsilateral visceral, mediastinal, or diaphragmatic
pleura
___ All ipsilateral pleural surfaces (including fissure)
___ Diaphragmatic muscle
___ Lung parenchyma
___ Endothoracic fascia
___ Mediastinal fat
___ Soft tissues of chest wall in a solitary focus
___ Soft tissues of chest wall diffusely or in multiple foci
___ Into but not through the pericardium
___ Rib(s)
___ Mediastinal organ(s) (specify): _________________
___ Other (specify): _________________
___ Cannot be determined: _________________
___ No evidence of primary tumor

Treatment Effect (Note F)

___ No known presurgical therapy
___ Not identified
___ Present
Percentage of Residual Viable Tumor
___ Specify percentage: _________________ %
___ Other (specify): _________________
___ Cannot be determined
___ Cannot be determined: _________________

+Tumor Comment: _________________

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MARGINS (Note G)

Margin Status
___ All margins negative for mesothelioma
___ Mesothelioma present at margin
Margin(s) Involved by Mesothelioma
___ Specify involved margin(s): _________________
___ Cannot be determined (explain): _________________
___ Other (specify): _________________
___ Cannot be determined (explain): _________________
___ Not applicable

+Margin Comment: _________________

REGIONAL LYMPH NODES

Regional Lymph Node Status

___ Not applicable (no regional lymph nodes submitted or found)
___ Regional lymph nodes present
___ All regional lymph nodes negative for tumor
___ Tumor present in regional lymph node(s)
Nodal Site(s) with Tumor (select all that apply)
___ Bronchopulmonary: _________________
___ Hilar: _________________
___ Ipsilateral mediastinal (including internal mammary, peridiaphragmatic, pericardial fat pad, or
intercostal nodes) : _________________
___ Contralateral mediastinal (including internal mammary, peridiaphragmatic, pericardial fat pad, or
intercostal nodes) : _________________
___ Supraclavicular : _________________
___ Other (specify): _________________
___ Cannot be determined: _________________
Number of Lymph Nodes with Tumor
___ Exact number (specify): _________________
___ At least (specify): _________________
___ Other (specify): _________________
___ Cannot be determined (explain): _________________
___ Other (specify): _________________
___ Cannot be determined (explain): _________________
Number of Lymph Nodes Examined
___ Exact number (specify): _________________
___ At least (specify): _________________
___ Other (specify): _________________
___ Cannot be determined (explain): _________________

+Regional Lymph Node Comment: _________________

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DISTANT METASTASIS

Distant Site(s) Involved, if applicable (select all that apply)

___ Not applicable
___ Non-regional lymph node(s): _________________
___ Other (specify): _________________
___ Cannot be determined: _________________

PATHOLOGIC STAGE CLASSIFICATION (pTNM, AJCC 8th Edition) (Note H)

Reporting of pT, pN, and (when applicable) pM categories is based on information available to the pathologist at the time the report
is issued. As per the AJCC (Chapter 1, 8th Ed.) it is the managing physician’s responsibility to establish the final pathologic stage
based upon all pertinent information, including but potentially not limited to this pathology report.

TNM Descriptors (select all that apply)

___ Not applicable
___ r (recurrent)
___ y (post-treatment)

pT Category
___ pT not assigned (cannot be determined based on available pathological information)
___ pT0: No evidence of primary tumor
___ pT1: Tumor limited to the ipsilateral parietal pleura with or without involvement of: visceral pleura;
mediastinal pleura; diaphragmatic pleura
___ pT2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic,
and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle;
extension of tumor from visceral pleura into the underlying pulmonary parenchyma
___ pT3: Describes locally advanced but potentially resectable tumor. Tumor involving all of the ipsilateral
pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura), with at least one of the
following features: involvement of the endothoracic fascia; extension into mediastinal fat; solitary
completely resectable focus of tumor extending into the soft tissues of the chest wall; nontransmural
involvement of the pericardium
___ pT4: Describes locally advanced technically unresectable tumor. Tumor involving all of the ipsilateral
pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura), with at least one of the
following features: diffuse extension or multifocal masses of tumor in the chest wall, with or without
associated rib destruction; direct transdiaphragmatic extension of tumor to the peritoneum; direct
extension of tumor to the contralateral pleura; direct extension of tumor to mediastinal organs; direct
extension of tumor into the spine; tumor extending through to the internal surface of the pericardium with
or without a pericardial effusion, or tumor involving the myocardium

pN Category
___ pN not assigned (no nodes submitted or found)
___ pN not assigned (cannot be determined based on available pathological information)
___ pN0: No regional lymph node metastases
___ pN1: Metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the internal
mammary, peridiaphragmatic, pericardial fat pad, or intercostal) lymph nodes
___ pN2: Metastases in the contralateral mediastinal, ipsilateral, or contralateral supraclavicular lymph
nodes

pM Category (required only if confirmed pathologically)

___ Not applicable - pM cannot be determined from the submitted specimen(s)
___ pM1: Distant metastasis present

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ADDITIONAL FINDINGS

+Additional Findings (select all that apply)

___ None identified
___ Asbestos bodies
___ Pleural plaque
___ Pulmonary interstitial fibrosis (specify pattern if discernable): _________________
___ Inflammation (specify type): _________________
___ Other (specify): _________________

SPECIAL STUDIES
Ancillary Studies (Note I)
+Immunohistochemistry (specify stains and results): _________________
+Histochemistry (specify stains and results): _________________
+Electron Microscopy (specify results): _________________
+Other Ancillary Studies (specify types and results): _________________

COMMENTS

Comment(s): _________________

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Explanatory Notes

A. Specimen
The International Association for the Study of Lung Cancer (IASLC) has developed an international
malignant plural mesothelioma (MPM) staging database that was designed to address the limitations of
the mesothelioma staging. Data analyses revealed that survival was significantly influenced by whether a
curative or palliative surgical procedure was performed (median survival 18 versus 12 months, p
<0.0001).1 Early stage (stage I) MPM resected by extraplural pneumonectomy (EPP) with curative intent
were associated with a median survival of 40 months, whereas those managed by
Pleurectomy/decortication (P/D) with curative intent had a median survival of 23 months.1 Type of surgical
procedure did not impact survival in higher stage disease. It was also noted that significant variations
regarding surgical nomenclature for procedures for MPM exist among thoracic surgeons.2 The
International Staging Committee of the IASLC and the International Mesothelioma Interest Group (IMIG)
recommended that P/D refer to removal of all macroscopic tumor involving the parietal and visceral
pleura and that the term extended P/D (or EPD) to be used to describe parietal and visceral pleurectomy
together with resection of the diaphragm and /or pericardium.2,3

References
1. Rusch VW, Giroux D, Kennedy C et al. Initial analysis of the International Association for the
Study of Lung Cancer mesothelioma database. J Thorac Oncol. 2012; 7:1631-1639.
2. Rice D, Rusch V, Pass H, et al. Recommendations for uniform definitions of surgical techniques
for malignant pleural mesothelioma: a consensus report of the International Association for the
Study of Lung Cancer International Staging Committee and the International Mesothelioma
Interest Group. J Thorac Oncol. 2011;16:1304-1312.
3. Pass H, Giroux D, Kennedy C, et al. The IASLC Mesothelioma Staging Project: improving staging
of a rare disease through international participation. J Thorac Oncol. 2016;11(12):2082-2088.

B. Histologic Type
For consistency in reporting, the histologic classification published by the World Health Organization
(WHO) is recommended.1 Mesotheliomas are classified as epithelioid, sarcomatoid (including
desmoplastic) or biphasic. Recognition and reporting of various architectural patterns, cytological features
and stromal features is encouraged because of their prognostic value.2 Desmoplastic mesothelioma is
considered to represent a variant of sarcomatoid mesothelioma. Biphasic mesotheliomas, contain both
epithelioid and sarcomatoid subtypes, and each component should represent at least 10% of the tumor.1

The 2021 WHO classification recommends using well-differentiated papillary mesothelial tumor (WDPMT)
over well-differentiated papillary mesothelioma (WDPM).1 These are noninvasive papillary neoplasms
associated with slow growth and recurrences. Survival is better than that for diffuse mesotheliomas.
WDPMTs are not staged according to AJCC staging system and do not require a synoptic report.

The 2021 WHO classification introduced the concept of mesothelioma in-situ as a preinvasive single-layer
surface proliferation of neoplastic mesothelial cells.1,3 The diagnosis may be suspected in patients with
recurrent effusions. The WHO considers essential diagnostic criteria to be (a) non-resolving pleural
effusion, (b) no thoracoscopic or imaging evidence of tumor, and (c) a single layer of mesothelial cells
(with or without atypia) on the pleural surface with loss of BAP1 and/or MTAP by immunohistochemistry
and/or CDKN2A homozygous deletion by fluorescence in-situ hybridization. Multidisciplinary discussion of
these cases is encouraged. Mesothelioma in-situ is not staged according to AJCC staging system and
does not require a synoptic report.

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References
1. WHO Classification of Tumours Editorial Board. Thoracic tumours. Lyon (France): International
Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 5).
https://publications.iarc.fr/595.
2. Nicholson AG, Sauter JL, Nowak AK, et al. EURACAN/IASLC Proposals for Updating the
Histologic Classification of Pleural Mesothelioma: Towards a More Multidisciplinary Approach. J
Thorac Oncol. 2020 Jan;15(1):29-49.
3. Churg A, Galateau-Salle F, Roden AC, et al. Malignant mesothelioma in situ: morphologic
features and clinical outcome. Mod Pathol. 2020 Feb;33(2):297-302.

C. Histologic Grade
The 2021 WHO classification recommends grading of diffuse epithelioid mesothelioma to identify tumors
that may behave aggressively.1 A nuclear grade is assigned based on nuclear atypia and mitotic count
and subsequently combined with the presence or absence of necrosis.2,3 Low grade tumors are those
exhibiting nuclear grade 1 (with or without necrosis) or nuclear grade 2 without necrosis. High grade
tumors are those exhibiting nuclear grade 2 with necrosis, or nuclear grade 3 with or without necrosis.

Grading should be performed based on the areas showing the highest-grade features.

References
1. WHO Classification of Tumours Editorial Board. Thoracic tumours. Lyon (France): International
Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 5).
https://publications.iarc.fr/595.
2. Rosen LE, Karrison T, Ananthanarayanan V, Gallan AJ, Adusumilli PS, Alchami FS, Attanoos R,
Brcic L, Butnor KJ, Galateau-Sallé F, Hiroshima K, Kadota K, Klampatsa A, Stang NL,
Lindenmann J, Litzky LA, Marchevsky A, Medeiros F, Montero MA, Moore DA, Nabeshima K,
Pavlisko EN, Roggli VL, Sauter JL, Sharma A, Sheaff M, Travis WD, Vigneswaran WT, Vrugt B,
Walts AE, Tjota MY, Krausz T, Husain AN. Nuclear grade and necrosis predict prognosis in
malignant epithelioid pleural mesothelioma: a multi-institutional study. Mod Pathol. 2018
Apr;31(4):598-606.
3. Nicholson AG, Sauter JL, Nowak AK, et al. EURACAN/IASLC Proposals for Updating the
Histologic Classification of Pleural Mesothelioma: Towards a More Multidisciplinary Approach. J
Thorac Oncol. 2020 Jan;15(1):29-49.

D. Tumor Focality
The majority of malignant mesotheliomas exhibit diffuse growth and may take the form of multiple small
nodules, plaque-like masses, or confluent rind-like sheets. However, a small proportion of malignant
mesotheliomas are sharply circumscribed. These are designated by the term “localized malignant
mesothelioma.” Localized malignant mesotheliomas appear to have a far better prognosis than their
diffuse counterpart.1

References
1. Marchevsky AM, Khoor A, Walts AE, et al. Localized malignant mesothelioma, an unusual and
poorly characterized neoplasm of serosal origin: best current evidence from the literature and the
International Mesothelioma Panel. Mod Pathol. 2020 Feb;33(2):281-296.

E. Tumor Extent
Invasion of the endothoracic fascia is categorized as T3. The endothoracic fascia is located external to
the parietal pleura beneath the muscles and ribs of the chest wall. Determining the presence or absence
of endothoracic fascial invasion can be difficult on pathologic examination, because the endothoracic
fascia lacks distinctive gross and histologic features. Assessment of the intactness of the endothoracic
fascia is best made by the surgeon at the time of operation.

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Although the American Joint Committee on Cancer (AJCC) designates a solitary focus of tumor invading
the soft tissues of the chest wall as T3, it does not specifically delineate the elements that constitute the
chest wall. According to the surgical literature, the constituents of the chest wall are the ribs, intercostal
muscles, and associated supporting connective tissues, the latter 2 of which can be inferred to represent
the chest wall soft tissues. Note that this definition does not include the layer of adipose tissue, which is
sometimes referred to as extrapleural fat, that lies between the chest wall and the parietal pleura. For
specimens that incorporate chest wall structures, it is recommended that the surgeon designate the
location(s) of such structures to ensure optimal pathologic assessment.

Although T4 describes locally advanced, technically unresectable tumor, radical extrapleural

pneumonectomy specimens may occasionally incorporate structures directly invaded by tumor that fall
under the T4 designation. These should be specified under “other” and include tumor extension to the
following:
- Peritoneum (through the diaphragm)
- Contralateral pleura
- Spine
- Internal surface of the pericardium
- Myocardium
- Brachial plexus

F. Treatment Effect
Induction chemotherapy or radiation before extrapleural pneumonectomy is being used in some centers
for locally advanced malignant pleural mesothelioma.1,2 Although a formal scheme for grading histologic
response to neoadjuvant treatment has not been established, in applicable specimens, the percentage of
residual viable tumor should be reported.

References
1. Flores RM, Krug LM, Rosenzweig KE, et al. Induction chemotherapy, extrapleural
pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant
pleural mesothelioma: a phase II trial. J Thorac Oncol. 2006;1:289-295.
2. Cho BC, Feld R, Leighl N, et al. A feasibility study evaluating Surgery for Mesothelioma After
Radiation Therapy: the 'SMART' approach for resectable malignant pleural mesothelioma. J
Thorac Oncol. 2014 Mar;9(3):397-402.

G. Margins
Because extrapleural pneumonectomy specimens are obtained by dissection of tumor from the thorax
with en bloc resection of the lung, pleura, pericardium, and diaphragm, the entire surface of the
extrapleural pneumonectomy represents the surgical margin (unless otherwise specified by the operating
surgeon).

H. Pathologic Stage Classification

This protocol recommends the AJCC and the International Union Against Cancer (UICC) TNM staging
system shown below.1,2 The changes introduced in the AJCC Cancer Staging Manual 8th edition are
based on analyses of the IASLC retrospective and prospective databases.3,4,5,6

By AJCC/UICC convention, the designation “T” refers to a primary tumor that has not been previously
treated. The symbol “p” refers to the pathologic classification of the TNM, as opposed to the clinical
classification, and is based on gross and microscopic examination. pT entails a resection of the primary
tumor or biopsy adequate to evaluate the highest pT category, pN entails removal of nodes adequate to
validate lymph node metastasis, and pM implies microscopic examination of distant lesions. Clinical

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classification (cTNM) is usually carried out by the referring physician before treatment during initial
evaluation of the patient or when pathologic classification is not possible.

Pathologic staging is usually performed after attempted surgical resection of the primary tumor.
Pathologic staging depends on pathologic documentation of the anatomic extent of disease, whether or
not the primary tumor has been completely removed. If a biopsied tumor is not resected for any reason
(eg, when technically infeasible) and if the highest T and N categories or the M1 category of the tumor
can be confirmed microscopically, the criteria for pathologic classification and staging have been satisfied
without total removal of the primary cancer.

TNM Descriptors
For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y,” “r,” and “a”
prefixes are used. Although they do not affect the stage grouping, they indicate cases needing separate
analysis.

The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in
parentheses: pT(m)NM. In actuality, this is not a descriptor that readily applies to diffuse malignant pleural
mesothelioma, which often exhibits a multinodular growth pattern but is best considered a single tumor for
staging purposes. Because of this, the “m” descriptor is not listed as an option in this protocol case
summary.

The “y” prefix indicates those cases in which classification is performed during or after initial multimodality
therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy).
The cTNM or pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of
tumor actually present at the time of that examination. The “y” categorization is not an estimate of tumor
before multimodality therapy (ie, before initiation of neoadjuvant therapy).

The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval and is
identified by the “r” prefix: rTNM.

Additional Descriptors

Residual Tumor (R)

Tumor remaining in a patient after therapy with curative intent (eg, surgical resection for cure) is
categorized by a system known as R classification, shown below.
RX Presence of residual tumor cannot be assessed
R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor

For the surgeon, the R classification may be useful to indicate the known or assumed status of the
completeness of a surgical excision. For the pathologist, the R classification is relevant to the status of
the margins of a surgical resection specimen. That is, tumor involving the resection margin on pathologic
examination may be assumed to correspond to residual tumor in the patient and may be classified as
macroscopic or microscopic according to the findings at the specimen margin(s).

References
1. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York, NY:
Springer; 2017.

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2. Brierley JD, Gospodarowicz MK, Wittekind C, et al, eds. TNM Classification of Malignant
Tumours. 8th ed. Oxford, UK: Wiley; 2016.
3. Pass H, Giroux D, Kennedy C, et al. The IASLC Mesothelioma Staging Project: improving staging
of a rare disease through international participation. J Thorac Oncol. 2016;11(12):2082-2088.
4. Nowak AK, Chansky K, Rice DC, et al. The IASLC Mesothelioma Staging Project: proposals for
revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for pleural
mesothelioma. J Thorac Oncol. 2016;11(12):2089-2099.
5. Rice D, Chansky K, Nowak AK, et al. The IASLC Mesothelioma Staging Project: proposals for
revisions of the N descriptors in the forthcoming eighth edition of the TNM classification for
pleural mesothelioma. J Thorac Oncol. 2016;11(12):2100-2111.
6. Rusch VW, Chansky K, Kindler HL, et al. The IASLC Mesothelioma Staging Project: proposals for
the M descriptors and for revision of the TNM stage groupings in the forthcoming (eighth) edition
of the TNM classification for mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2112-2119

I. Ancillary Studies
Immunohistochemistry is required for a definitive diagnosis of malignant mesothelioma. The
immunohistochemical approach depends on the mesothelioma morphology (epithelioid, sarcomatoid) and
the type of tumors that are considered in the differential diagnosis. The 2021 WHO classification
continues to recommend the combined use of a minimum of two mesothelial markers and two carcinoma
markers.1 Based on the specificity and sensitivity, the best positive mesothelial markers include calretinin,
cytokeratins 5/6, WT-1, and D2-40. BerEP4 or MOC31, B72.3, CEA, and BG8 are the most frequently
used to diagnose carcinoma.1 No specific panel is recommended, and the International Mesothelioma
Panel recommends that each laboratory should choose antibodies with a sensitivity and specificity of at
least 80%.2 The College of American Pathologists does not endorse a specific panel of markers for the
evaluation of malignant mesothelioma. If sarcoma is considered in the differential diagnosis appropriate
immunohistochemical, cytogenetic and molecular workup should be performed. Diagnostic role of
histochemistry and electron microscopy is very limited because immunohistochemistry is widely available
and frequently sufficient to establish the diagnosis of malignant mesothelioma.

References
1. WHO Classification of Tumours Editorial Board. Thoracic tumours. Lyon (France): International
Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 5).
https://publications.iarc.fr/595.
2. Husain AN, Colby TV, Ordonez N, et al. Guidelines for pathologic diagnosis of malignant
mesothelioma: 2017 update of the consensus statement from the International Mesothelioma
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